Methyldopa

Registered South African indications:

• Essential hypertension

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Impaired kidney or liver function or with a history of liver disease
• Mental depression
• Acute liver disease
• Phaeochromocytoma
• Methyldopa has been reported to aggravate porphyria
• Coadministration with monoamine oxidase inhibitors (MAOI) (500mg tab)

Contraindications registered in other jurisdictions

• Hypersensitivity to the active substance (including hepatic disorders associated with previous methyldopa therapy), or to any of its excipients
• Active hepatic diseases, such as acute hepatitis and active cirrhosis
• Depression
• Coadministration with monoamine oxidase inhibitors
• Catecholamine-secreting tumor such as phaeochromocytoma or paraganglioma
• Porphyria

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment (Recommendations in other jurisdictions)
• Elderly
• Bilateral cerebrovascular disease
• History hepatic disease (Recommendations in other jurisdictions)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: fct

South African registered indications and dosages

Essential hypertension

• Oral (fct): Initial: 250mg, 2-3 times daily for the first 48hrs; Titration: Adjust the dose at intervals of not less than 48hrs until adequate response achieved; Usual dose: 500mg to 2g daily

Paed. forms avail. in SA and covered in this monograph: fct

South African registered indications and dosages

Essential hypertension

• Oral (fct): Initial: 10mg/kg body mass, daily in divided doses

Pregnancy

South African recommendations

• Caution
• The safety of methyldopa in pregnancy has not been established, as there are no adequate and well-controlled studies in pregnant women
• Methyldopa crosses the placenta and reduced blood pressure has been reported in infants born to mothers receiving methyldopa

Recommendations in other jurisdictions

• Caution
• Methyldopa has been used under medical supervision for the treatment of hypertension during pregnancy. There is no clinical evidence of foetal abnormalities or effect on the neonate.  Published reports of the use of methyldopa during all trimesters indicate that if this drug is used during pregnancy the possibility of foetal harm appears remote. Methyldopa crosses the placental barrier and is present in cord blood
• Although no obvious teratogenic effects have been reported, the possibility of foetal injury cannot be excluded and the use of methyldopa in women who are, or may become, pregnant requires that anticipated benefits be weighed against possible risks

Breastfeeding

South African recommendations

• Caution
• Methyldopa is distributed into breast milk in small amounts. The safety of methyldopa in lactation has not been established

Recommendations in other jurisdictions

• Caution
• Methyldopa appears in breast milk. The use of methyldopa in breastfeeding mothers requires that anticipated benefits be weighed against possible risks

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No information available

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Caution; dose adjustment recommended

Please note that the use of antihypertensives in patients needing continuous renal replacement therapy (CRRT) is generally discouraged. CRRT is usually utilised when patients cannot tolerate intermittent hemodialysis due to hypotension

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated

South African recommendations

• Caution; no information available

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Initial: 125mg, 12hrly; Max: 250mg/day; Titrate gradually; Max maintenance dose: 2g/day
  Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses

Central Nervous System Disorders

• Nightmares
• Reversible mild psychoses
• Depression 
• Sedation
• Headache
• Paraesthesia
• Parkinsonism
• VIIth nerve paralysis
• Choreoathetosis
• Mental impairment
• Carotid sinus syndrome
• Dizziness
• Cerebrovascular insufficiency
• Aesthenia

Cardiovascular Disorders

• Bradycardia
• Angina pectoris
• Myocarditis
• Pericarditis
• Atrioventricular block
• Orthostatic hypotension
• Oedema

Respiratory Disorders

• Nasal congestion

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal distension
• Constipation
• Flatulence
• Diarrhoea
• Colitis
• Dry mouth
• Glossodynia
• Tongue discolouration
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis
• Jaundice
• Abnormal liver-function tests

Genitourinary Disorders

• Increased serum urea levels

Endocrine and Metabolic Disorders

• Decreased libido
• Hyperprolactinaemia
• Breast enlargement
• Gynaecomastia
• Amenorrhoea
• Lactation disorder
• Erectile dysfunction
• Ejaculation failure
• Positive Coombs test
• Positive tests for antinuclear antibody
• Positive test for LE cells
• Positive test for rheumatoid factor

Musculoskeletal Disorders

• Lupus-like syndrome
• Mild arthralgia with or without joint swelling
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash (eczema, lichenoid eruption)
• Toxic epidermal necrolysis
• Angioedema
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Sialoadenitis
• Haemolytic anaemia
• Bone-marrow failure
• Leukopenia
• Granulocytopenia
• Thrombocytopenia
• Eosinophilia
• Pyrexia

• Diuretics
• Antihypertensive agents
• Beta blockers
• Antidepressant drugs
• Anaesthetic agents
• Halothane
• Lithium
• Sympathomimetics
• Phenothiazines
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Phenothiazines
• Ferrous sulphate
• Ferrous gluconate

None routine. Specific cases may require

• Full blood count
• Hepatic function
• Coombs test

The mechanism of action has yet to be conclusively demonstrated, however the hypotensive effect is most likely due to the drug's action on the central nervous system. Methyldopa is converted into alpha-methylnorepinephrine, which stimulates the central inhibitory alpha-adrenergic receptors. This leads to a reduction in sympathetic tone, total peripheral resistance, and blood pressure. Reduction in plasma renin activity, as well as the inhibition of both central and peripheral norepinephrine and serotonine production may also contribute to the drug's antihypertensive effect.

Capsule 250mg 

• Normopress (Alliance) originator

Tablet 250mg

• Hypotone (Pharmacare)
• Methyldopa Ascendis 250 (Dezzo trading)
• Mylan Methyldopa (Mylan)
• Sandoz Methyldopa (Sandoz)

Tablet 500mg

• Hypotone (Pharmacare)